Shiyang Li

The local environment may affect the development and function of tissue-resident T regulatory cells (Tregs), which are crucial for controlling inflammation. Although the aryl hydrocarbon receptor (Ahr), an environmental sensor, is expressed by Tregs, its role in Treg cell development and/or function remains elusive. Here, we generated mouse genetic models to ablate or activate Ahr expression specifically in Tregs. We showed that Ahr was expressed more abundantly by peripherally induced Tregs (pTregs) in the gut and that its expression was independent of microbiota. Ahr was important for Treg gut homing and function. Ahr inhibited pro-inflammatory cytokines produced by Tregs but was dispensable for Treg stability. Furthermore, Ahr-expressing Tregs had enhanced in vivo suppressive activity compared with Tregs lacking Ahr expression in a T cell transfer model of colitis. Our data suggest that Ahr signaling in Tregs may be important for gut immune homeostasis.

With striking similarity to their adaptive T helper cell counterparts, innate lymphoid cells (ILCs) represent an emerging family of cell types that express signature transcription factors, including T-bet+ Eomes+ natural killer (NK) cells, T-bet+ Eomes– group 1 ILCs (ILC1), GATA3+ group 2 ILCs (ILC2), RORγt+ group 3 ILCs (ILC3), and newly identified Id3+ regulatory ILC (ILCreg). ILCs are abundantly present in barrier tissues of the host (e.g., the lung, gut, and skin) at the interface of host-environment interactions. Active research has been conducted to elucidate molecular mechanisms underlying the development and function of ILCs. The aryl hydrocarbon receptor (Ahr) is a ligand-dependent transcription factor, best known to mediate the effects of xenobiotic environmental toxins and endogenous microbial and dietary metabolites. Here we review recent progresses regarding Ahr function in innate lymphoid cells. We focus on the Ahr-mediated cross-talk between ILCs and other immune/non-immune cells in host tissues especially in the gut. We discuss the molecular mechanisms of the action of Ahr expression and activity in regulation of ILCs in immunity and inflammation, and the interaction between Ahr and other pathways/transcription factors in ILC development and function with their implication in disease.

A novel dual-signal fluorometric and colorimetric probe FMDH (5-FAM-Met-Asp-His-NH2), incorporating a tripeptide (Met-Asp-His-NH2) linked to 5-carboxyfluorescein (5-FAM), was firstly synthesised. FMDH demonstrated exceptional selectivity and sensitivity, rapid response, wide pH response range and robust anti-interference capabilities for monitoring Cu2+. This was achieved through a distinctive naked-eye colorimetric and fluorescent quenching behaviour. A good linearity within the range of 0–3 μM (R2 = 0.9914) was attained, and the limit of detection (LOD) for Cu2+ was 47.4 nM. Furthermore, the FMDH-Cu2+ ensemble responded to glyphosate with notable selectivity and sensitivity. A good linear correlation (R2 = 0.9926) was observed at the lower concentration range (2.4–7.8 μM) and achieving a detection limit as low as 29.9 nM. The response time of FMDH with Cu2+ and glyphosate were less than 20 s, and the pH range of 7–11 that was suitable for practical application under physiological pH conditions. MTT assays confirmed that FMDH offers good permeability and low toxicity, facilitating successful application in imaging analysis of Cu2+ and glyphosate in living cells and zebrafish. In addition, FMDH was employed in the detection of these analytes in real water samples. Cost-effective, highly sensitive and easily prepared FMDH-impregnated test strips were developed for the efficient visual detection of Cu2+ and glyphosate under 365 nm UV light. Increasing concentrations of Cu2+ and glyphosate resulted in notable colour changes under 365 nm UV light, enabling visual semi-quantitative analysis via a smartphone colour-analysis App.